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Mutations in the SLC34A2 Gene Are Associated with Pulmonary Alveolar Microlithiasis

Departments of Respiratory Medicine, Pathology, and Chest Surgery, Saitama Medical University, Saitama; Department of Respiratory Oncology and Molecular Medicine, Tohoku University, Sendai; Department of Pulmonary Medicine, Disease Control and Prevention Center, International Medical Center of Japan; Department of Respiratory Medicine, Tama Hokubu Hospital; Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo; Department of Cardiovascular Pharmacology, Yamagata University, Yamagata; Department of Respiratory Medicine, Katta General Hospital, Miyagi; Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama; Third Department of Internal Medicine, Sapporo Medical University, Sapporo; Department of Surgery II, Fukushima Medical University, Fukushima; Clinical Research Center, National Hospital Organization, Kinki-chuo Chest Medical Center; and Osaka Kampo Medical Center, Osaka, Japan

Correspondence and requests for reprints should be addressed to Koichi Hagiwara, M.D., Ph.D., Professor, Department of Respiratory Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350–0495, Japan. E-mail: hagiwark{at}saitama-med.ac.jp

Rationale: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space.

Objectives: To identify the responsible gene that causes pulmonary alveolar microlithiasis.

Methods: By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis.

Measurements and Main Results: We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function.

Conclusion: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

Key Words: pulmonary alveolar microlithiasis • homozygosity mapping • GeneChip • single-nucleotide polymorphisms

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. However, the responsible gene has not been identified. What This Study Adds to the Field Mutation of the SLC34A2 gene that encodes the sodium-dependent phosphate transporter causes pulmonary alveolar microlithiasis.

 

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